| Formation of a fairly stable diazoate intermediate of 5-methyl-2'-deoxycytidine by HNO2 and NO, and its implication to a novel mutation mechanism in CpG site. | |
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MedLine Citation:
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PMID: 11836116 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The intermediate produced from 5-methyl-2'-deoxycytidine ((5me)dCyd) by HNO2 and NO treatments was isolated and characterized. When 10mM (5me)dCyd was incubated with 100mM NaNO2 at pH 3.7 and 37 degrees C, a previously unidentified product was formed. The product was identified as a diazoate derivative of (5me)dCyd, 1-(beta-D-2'-deoxyribofuranosyl)-5-methyl-2-oxopyrimidine-4-diazoate ((5me)dCyd-diazoate), on the bases of several measurements including LC/MS. The time course of the concentration change of the diazoate showed a characteristic profile of a reaction intermediate, and the steady state concentration was 2.3 microM (0.023% yield). When an aqueous solution of 10mM (5me)dCyd (10 mL) was bubbled by NO at 37 degrees C under aerobic conditions holding the pH around 7.4, the diazoate was also generated. The yield of the diazoate was 0.041 micromol (0.041% yield) at 20 mmol of NO absorption. At physiological pH and temperature (pH 7.4, 37 degrees C), the diazoate was converted to dThd exclusively with a first order rate constant k=9.1x10(-6) x s(-1) (t(1/2)=21 h). These results show that the diazoate is generated as a relatively stable intermediate in the reactions of (5me)dCyd with HNO2 and NO and further suggest that the diazoate can be formed in cellular DNA with biologically relevant doses of HNO2 and NO. |
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Authors:
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Toshinori Suzuki; Masaki Yamada; Takanori Nakamura; Hiroshi Ide; Kenji Kanaori; Kunihiko Tajima; Takashi Morii; Keisuke Makino |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Bioorganic & medicinal chemistry Volume: 10 ISSN: 0968-0896 ISO Abbreviation: Bioorg. Med. Chem. Publication Date: 2002 Apr |
Date Detail:
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Created Date: 2002-02-11 Completed Date: 2002-09-11 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9413298 Medline TA: Bioorg Med Chem Country: England |
Other Details:
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Languages: eng Pagination: 1063-7 Citation Subset: IM |
Affiliation:
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Institute of Advanced Energy, Kyoto University, Gokasho, 611-0011, Uji, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Azo Compounds
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chemistry,
metabolism* DNA / drug effects, genetics, metabolism Deoxycytidine / analogs & derivatives*, chemistry, genetics, metabolism* Deoxycytosine Nucleotides / chemistry, genetics, metabolism Deoxyguanosine / analogs & derivatives*, chemistry, genetics, metabolism Dinucleoside Phosphates / metabolism Drug Stability Kinetics Models, Genetic Molecular Structure Mutation Nitric Oxide / metabolism* Nitrous Acid / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Azo Compounds; 0/Deoxycytosine Nucleotides; 0/Dinucleoside Phosphates; 10102-43-9/Nitric Oxide; 15178-66-2/deoxycytidylyl-(3'-5')-deoxyguanosine; 2382-65-2/cytidylyl-3'-5'-guanosine; 7782-77-6/Nitrous Acid; 838-07-3/5-methyldeoxycytidine; 9007-49-2/DNA; 951-77-9/Deoxycytidine; 961-07-9/Deoxyguanosine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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